The present invention relates to an apparatus and process for dispensing and printing reagent fluids, wherein a transducer is used to propel small quantities of the fluid towards a positioned target.
Diagnostic assays often require systems for metering, dispensing and printing reagent fluids. In the case of metering and dispensing, such systems comprise both manual and automatic means. For purposes of practicality, the present background discussion will focus on the methods of metering and dispensing 100 micro-liter volumes or less.
The manual systems of metering and dispensing include the glass capillary pipet; the micro-pipet; the precision syringe; and weighing instruments. The glass capillary pipet is formed from a precision bore glass capillary tube. The pipet typically comprises a fire blown bulb and a tubular portion fire drawn to a fine point. Fluid is precisely metered by aspirating liquid through the tube into the bulb to a predetermined level indicated by an etched mark. The fluid may then be dispensed by blowing air through the tube.
The micro-pipet typically comprises a cylinder and a spring loaded piston. The travel of the piston is precisely determined by a threaded stop. The distance the piston travels within the cylinder and the diameter of the cylinder define a precise volume. The fluid is aspirated into and dispensed from the micro-pipet in precise quantities by movement of the piston within the cylinder.
The precision syringe generally comprises a precisely manufactured plunger and cylinder with accurately positioned metering marks. The fluid is introduced into and dispensed from the syringe by movement of the plunger between the marks.
Weighing techniques for dispensing fluids often simply involve weighing a quantity of fluid. The density of the fluid may then be used to determine the fluid volume.
Exemplary automatic metering and dispensing systems include the precision syringe pump; the peristaltic pump; and the high performance liquid chromatography (HPLC) metering valve. The precision syringe pump generally comprises a precision ground piston located within a precision bore cylinder. The piston is moved within the cylinder in precise increments by a stepping motor.
The peristaltic pump comprises an elastmeric tube which is sequentially pinched by a series of rollers. Often the tube is placed inside a semicircular channel and the rollers mounted on the outer edge of a disc driven by a stepping motor. The movement of the rollers against the tubing produces peristaltic movement of the fluid.
The HPLC metering valve comprises a defined length of precision inner diameter tubing. The fluid is introduced into the defined volume of the tubing with the valve in a first position and then dispensed from the tubing when the valve is placed in a second position.
All of the above metering and dispensing systems have the disadvantage that the volumes dispensed are relatively large. Furthermore, these systems are also relatively slow, inefficient and comprise precision fitted components which are particularly susceptible to wear.
The printing of reagent fluids is frequently required in the manufacture of chemical assay test strips. Selected reagents are printed in a desired configuration on strips of filter paper. The strips may then be used as a disposable diagnostic tool to determine the presence or absence of a variety of chemical components.
Generally, to perform a chemical assay with a test strip, the strip is exposed to a fluid or a series of fluids to be tested, such as blood, serum or urine. In some instances, the strip is rinsed and processed with additional reagents prior to being interpreted. The precise interpretation depends on the type of chemical reactions involved, but may be as simple as visually inspecting the test strip for a particular color change.
The manufacture of test strips generally involves either a printing process or a blotting process. The blotting process is the simplest manufacturing method and permits most reagents to be applied without modification. A disadvantage of this process is that it is difficult to blot the fluids onto the test strip with precision.
The printing process will often involve any of three well known methods silk screening; gravure; and transfer printing. The silk screening of reagents generally involves producing a screen by photographic methods in the desired configuration for each reagent to be printed. The screen is exposed under light to a preselected pattern and then developed. The areas of the screen which are not exposed to light, when developed, become porous. However, the areas of the screen which have been exposed to light remain relatively nonporous. The screen is then secured in a frame and the test strip placed below. The desired reagent fluid, specially prepared to have a high viscosity, is spread over the top side of the screen. The reagent passes through the porous areas of the screen and onto the test strip. The test strip is then subjected to a drying process, specific to each reagent. Once the test strip is dry, it may be printed again using a different screen, pattern and reagent.
The gravure method of printing reagents comprises coating a metal surface with a light sensitive polymer. The polymer is exposed to light in the desired predetermined pattern. When developed, the polymer creates hydrophilic and hydrophobic regions. The reagent is specially prepared such that when applied to the metal it will adhere only to the hydrophilic regions. After the specially prepared reagent is applied, the test strip is pressed against the metal and the reagent is transferred from the metal to the test strip.
The transfer printing method comprises transferring the reagents from a die to the test strip in the desired pattern. The die is made with the appropriate pattern on its surface and then coated with the desired, specially prepared reagent. A rubber stamp mechanism is pressed against the die to transfer the reagent in the desired pattern from the die to the rubber stamp. The rubber stamp is then pressed against the test strip to transfer the reagent, in the same pattern, to the test strip.
Each of the above-mentioned reagent printing techniques has significant disadvantages. The most common disadvantage is the requirement that the reagents must be specially prepared. Additionally, if a variety of reagents are to be printed onto a single test strip, the strip must be carefully aligned prior to each printing. This alignment procedure increases the cost and decreases the throughput of the printing process. Moreover, a special die or screen must be produced for each pattern to be printed. A further disadvantage arises in that the above printing methods are unable to place reproduceable minute quantities of reagent on the test strip.
It is an object of the present invention to provide a printing and dispensing method and apparatus which avoids these disadvantages.